Through the studies outlined here we hope to explore alterations in glycoprotein formation, structure, and function in transformed and malignant cells. Emphasis will be placed on further investigation of a distinctive galactosyltransferase (designated galactosyltransferase isoenzyme II, GT-II) associated with both clinical malignancy and in vitro transformation. Both GT-II and a normal galactosyltransferase isoenzyme (GT-I) have been purified to homogeneity. We have now produced antibodies to human GT-I and GT-II and are in the process of developing a prototype radioimmunoassay to facilitate more extensive evaluation and widespread use of GT-II measurement as well as in situ localization of GT-II in the transformed cell. We have described cancer-associated glycopeptide (CAG) in sera of patients with extensive metastatic cancer which specifically inhibits growth of transformed cells and reduces tumor growth in animal models. We have explored the kinetics of CAG attachment to transformed cells with tritiated CAG and are purifying the cellular CAG-receptor from transformed cells. The effects of CAG on intermediate carbohydrate metabolism are currently under investigation. The mechanism of CAG tumor growth inhibition and its potential use as an antineoplastic agent are being studied with a variety of animal tumor models. In related studies a tumor-promoting growth factor (TGF) isolated from some human malignant effusions has been found to block the growth inhibitory activity of CAG. The relationship between TGF and CAG and the mechanisms of their activities is undergoing further study. (A)